This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Diabetic nephropathy is a devastating complication of diabetes mellitus and its pathogenesis remains unclear. Evidence from experimental animal models indicates that diabetes is associated with an early activation of the renal tissue renin-angiotensin system even when the systemic renin-angiotensin system is suppressed. In addition, clinical studies have shown that blockade of the renin-angiotensin system delays progression from mild to end-stage renal disease, and angiotensin blockers now constitute standard therapy in diabetic subjects with microalbuminuria. We have developed an assay for human angiotensinogen, the only known precursor of angiotensin, in human urine for the first time. This study tests whether measurement of urinary angiotensinogen can serve as a marker for the activity of the local kidney renin-angiotensin system and whether, how early and to what extent urinary angiotensinogen levels are elevated in type-2 diabetes mellitus. This study anticipates that urinary angiotensinogen measurement in diabetic human subjects can predict the extent of kidney damage and can be employed to identify subjects in whom blockade of the renin-angiotensin system would be beneficial.